A). The past decade has witnessed the discovery of thirty or more peptides localized in mammalian central neurons. Cholecystokinin (CCK) a gut peptide was recently found in microgram concentrations in cerebral cortex, limbic structures, and spinal cord. Cholecystokinin appears to coexist with dopamine in the mesolimbic pathway from ventral tegmentum to nucleus accumbes and olfactory tubercle. Behavioral techniques provide useful tools for elucidating the mechanism of neuromodulation of a known neurotransmitter by a peptide. Understanding of CCK modulation of dopamine may lead to the development of more specific and effective antipsychotic treatments. Animal studies have focused on anatomical sites of co-existence of cholecystokinin and dopamine (DA). In the nucleus accumbens, CCK potentiated the behavioral effects of DA and the dopaminergic agonists, apomorphine (APO). CCK did not potentiate the behavioral effects of DA and APO when injected into the caudate nucleus, where CCK and DA do not coexist. Specific antagonists of CCK, e.g. proglumide, benzotript, and CCK antibody, blocked the ability of CCK to potentiate DA-induced behaviors. These results suggest that CCK acts to modulate dopaminergic function in the mesolimbic pathway. B). Gastrointestinal CCK has profound effects on feeding and exploratory behaviors, which have been characterized as the induction of a syndrome of "satiety". We are tracing the sensory feedback pathway from the gastrointestinal CCK receptors to brain regions which mediate feeding and exploration in rats. Lesions of the paraventricular nucleus of the hypothalamus, which receives rostral projections from the nucleus tracus solitarius, abolished the behavioral effect of CCK. One mechanism by which CCK induces satiety appears to require a sensory feedback pathway: GI tract Greater than vagus nerve Greater than nucleus tractus solitarius Greater than rostral fibers Greater than paraventricular nucleus of the hypothalamus.